In a conventional ophthalmic ointment, pharmaceutically active substances are suspended in petrolatum and mineral oil. Because the eye rejects oily fluids, however, a portion of the ointment is expelled upon application. Also, release of the active ingredient is delayed for the time required for water from the eye fluid to be exchanged with the ointment. As a result, only an inexact dose of active ingredient reaches the eye.
Furthermore, conventional ointments interfere with vision once they are applied, causing blurring. It is, for example, often required that activities of an individual be restricted until vision becomes clear after administration of an ophthalmic ointment.
While ointments exhibit some time release properties, these properties are unpredictable. The ointment is rejected in large part from the eye before a significant amount of the active ingredient is transferred to the aqueous phase.
Ophthalmic solutions suffer from similar deficiencies, as they run out of the eye upon administration. Thus, with such solutions only a low, imprecise amount of active reaches the eye. Also, solutions are generally applied to the center of the eye, where they cause blurring. For example, solutions are available for treating dry eye which contain small amounts of cellulose based additives as the active ingredient for lubricating the eye. Such products are available commercially containing 0.5% or 1% carboxymethyl cellulose and are known as "artificial tear preparations" or "lubricating eye drops". They form an occlusive film over the outer surface of the eye to protect it from drying and are used in particular to relieve dry eye associated with contact lens use. Such solutions have a low viscosity, i.e., substantially less than 10,000 cps (Brookfield LV at about 25.degree. C.). They are applied directly to the center of the eye, i.e., to the contact lens, causing blurring. They also deliver an imprecise amount of active.
Formulations for "longer lasting" relief of dry eye are available as ointments. One such preparation is formulated from 80% white petrolatum and 20% mineral oil. Such products, however, are easily expelled from the eye and offer only relatively short term relief, i.e., not more than about 30 minutes.
Inserts are available for ophthalmic use that are formed from solid cellulose. For example, U.S. Pat. No. 5,229,128 describes rods formed of methylcellulose for insertion into the eye to treat dry eye. They are formed from powdered cellulose derivative, dried, and then preferably placed in a gelatin capsule. To administer the solid rod, the ends of the gelatin capsule are separated, the rod being kept in one segment of the capsule, the inferior cul-de-sac of the eye is withdrawn, and the rod is dropped into the lower part of the eyelid. This is a difficult procedure, and for some patients requires the assistance of a physician. If no gelatin capsule is employed, forceps must be used to administer the insert. Furthermore, the solid cellulose of the insert needs to be wetted in the eye by eye fluid. The cellulose then swells, causing a possibility of irritation from undissolved crystals in the wetted cellulose. Also, wetting of the solid cellulose to form a gel in the eye occurs in an inconsistent manner from one individual to the next. It is also difficult to incorporate additional lubricating agents in such inserts, as any additional active product may crystalize in the eye, causing possible injury.
Solid inserts which suffer from the same deficiencies are also described in U.S. Pat. No. 4,343,787.
There is therefore a need for a safe ophthalmic formulation that is not easily expelled from the eye after administration, that delivers a precise dosage, that is easy to administer, and that is capable of controlled release of a pharmaceutically active substance.